Pharmaceutical compositions and medicaments typically are orally ingested in liquid, tablet, and capsule form. The gelatin capsule is a solid, oral dosage form of medicament generally consisting of two prefabricated cylindrical shells (a cap and a body), one end of each of which is rounded and closed, and the other end of which is open. A medicament or medicaments, usually in paste, liquid, or powder, are filled into the body which is then joined with a cap in order to close the capsule.
Historically, the hard gelatin capsule form of medication has been considered a preferred dosage form since patients perceive them as having no aftertaste, being easy to swallow, causing no indigestion, and working quickly. Although the gelatin capsule is a highly effective form of solid oral dosage for medications, recent events have focused attention on their security and tamper-resistance.
The standard gelatin capsule in which the smooth side wall of the body of the capsule is telescopically received within the smooth cylindrical side wall of the cap can be easily reopened after filling. One solution to prevent reopening after filling is to band the joined cap and body of each capsule at their seam of overlap with a gelatin band or film. This requires contact of each capsule by a liquid gelatin-coated roller to apply the band thereto, involves a time-consuming operation and costly apparatus, and is generally incompatible with high-speed capsule-filling machine operations.
As an alternative to capsule-banding to secure the cap and body portions, the smooth side walls of the cap and body of capsules have been shape-modified by provision of mating circular grooves and ridges to achieve a snap-fit securement of the cap and body to resist reopening after joining. Capsules having structurally-modified cap and body wall configurations are commercially available and sold by Capsugel Division of Warner Lambert Corporation under the trademarks Snap-Fit.TM., Coni-Snap.TM., and Coni-Snap Supro.TM..
While shape-modified cap and body structures which provide snap-fit securement greatly reduce splitting and denting effects during capsule joining, and make capsules more difficult to open after joining, tamper-resistance and security of capsules may be further improved by sealing the caps to the bodies after filling. Various techniques have been employed in sealing hard gelatin capsules, such as immersion of the capsules in a liquid sealing composition, specific application of a sealing composition to the capsule, cap spraying, mechanical thermal welding, gelatin banding, and through-hole spraying.
The most effective sealing of capsules is believed achieved by using a sealing fluid that results in a one-piece gelatin capsule. One commercially-available method for sealing hard gelatin capsules so that they cannot be opened without visible destruction is known as the Licaps.TM. sealing process developed by Capsugel. The Licaps.TM. process involves wetting the wall contact areas between the cap and body with a special melting-point-lowering liquid. After removal of the excess wetting liquid from the capsule, the sections are then thermally bonded into one unit. To obtain a homogeneous seal, it is important that the wall contact areas be exposed uniformly to the wetting liquid, which is achieved through capillary action, causing the wetting liquid to be drawn into the area between the overlapping walls of the cap and body of the capsule.
The wetting liquids are believed to act to dissolve the amorphous part of the gelatin between the overlap of the cap side walls over the body side walls of the capsules by lowering the glass transition temperature of the gelatin. Furthermore, the sealing or wetting liquids may depress the melting point of the crystalline part of the gelatin. Such wetting liquids must be readily ingestible, available, affect a lowering of the gelatin melting point, and have a small contact angle with the capsule walls to promote high capillary action. A number of such wetting liquids and their methods of application to capsules are disclosed and described in U.S. Pat. No. 4,539,060 to Wittwer et al. and in co-pending U.S. patent application Ser. No. 06/582,364 filed Feb. 22, 1984 now U.S. Pat. No. 4,656,066, both commonly-assigned with the present application. A highly suitable wetting liquid is a mixture of water and an alcohol, such as ethanol, two solvents which are frequently and commonly used in the manufacture of pharmaceutical products. The selection of the ratio of the liquid components of the wetting liquid depends upon the composition of the capsule wall (degree of moisture, presence of additives, such as dyes and pigments), the type of printing on the capsule, and the temperature during application of thermal energy. The disclosures of aforesaid U.S. Pat. Nos. 4,539,060 and 4,656,066 are incorporated herein by reference.
The Licaps.TM. capsule-sealing process is a three-step method involving a first liquid-contacting phase in which filled and closed gelatin capsules are brought into contact for a brief period of time with the wetting liquid, which is immediately distributed through capillary action into the area between the overlapping walls of the caps and bodies.
In the second step, or phase, excess wetting liquid is removed from the exposed outer walls of the conveyed capsules by mechanically draining and air-drying. The overlapping gelatin wall sections remain moist which causes the walls to swell, resulting in a homogeneous, though preliminary, seal between the cap and body.
In the third step, or phase, final and complete sealing is achieved by application of the specific amount of thermal energy to effect sealing.
Apparatus designed for practice of the Licaps.TM. sealing process consists of a sealing machine which may be linked by conveyor to receive filled capsules directly from a capsule-filling machine. The sealing machine comprises a rotating conical wire-mesh basket in which a wetting liquid is sprayed onto the entire outer surface of capsules as they are continuously fed therethrough. Capillary action causes transfer of some of the wetting liquid to the area between the overlapping walls of the cap and body of each capsule. The excess wetting liquid is removed from the capsules as they approach the exit end of the basket both by mechanical drainage and application of room-temperature air. From the liquid applicator basket, the capsules are directed alternately, in batch-wise manner, into one of two drying and sealing chambers which are in the form of fluidized beds. Since two chambers are available, the sealing machine operates to fill the chambers in alternating fashion, so that conditioned cool air is first passed through each chamber during capsule-filling to further dry the capsules, while heated air is thereafter passed through each chamber after it is filled to thermally seal the capsules. The excess wetting liquid, generally comprising a mixture of water and alcohol, which is removed from the capsules by drainage and evaporation, is eventually collected and processed by special recovery equipment to meet environmental regulations and requirements for disposal.
Although the Licaps.TM. capsule-sealing process and apparatus, as described, provides an effective method and means to produce a one-piece capsule which may not be separated without destruction, it does require rather specialized equipment for conveying, spraying, handling, treating, and initially drying the capsules which involves a considerable capital investment. Further, the application of a wetting liquid to the entire capsule outer body surface involves use of excess chemicals and additional costs in the necessary equipment to collect and dispose of the excess wetting chemicals to meet environmental standards and regulations.
In the aforementioned U.S. Pat. Nos. 4,539,060 and 4,656,066, it has been suggested that wetting liquids of the type described might be applied locally to seam areas of gelatin capsules for migration between the overlapping cap and body by delivering metered quantities of the wetting liquid by high-frequency pulsation of jets or nozzles.